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EC22-002: Is platelet Toll-like receptor 4 the silent partner of thrombosis in cats with hypertrophic cardiomyopathy? Investigating the immunothrombotic interactions between histones and platelets

Hypertrophic cardiomyopathy (HCM) is a heart disease that affects 1 in 7 cats. Cats with HCM are at risk of inappropriate blood clot formation that disrupts blood supply to the rear limbs, causes excruciating pain, and results in the death or euthanasia of a majority of afflicted cats. Despite drugs that aim to prevent clot formation like clopidogrel, the return of this condition is common. In addition, some cats with a known genetic mutation show drug resistance to clopidogrel. Therefore, there is a critical need for developing new anti-clotting drugs. In the pathway of blood clot formation, the interaction of white blood cells and platelets is crucial and represents a potential new target for anti-clotting treatments in cats. We propose that histone, a protein that is released by white blood cells, binds to and activates platelets in cats via a special receptor called Toll-Like Receptor-4 (TLR4). We seek to isolate and confirm this pathway of platelet activation first in healthy cats. Next, we will enroll cats with or without HCM to compare the production of these receptors in their platelets. We propose that cats with HCM are prone to clotting due to increased production of platelet TLR4. If our theory is proven to be true, we will identify a pathway that can be targeted with novel drugs to prevent or treat these deadly feline blood clots.

(Ricky Fund)

Grant ID: EC22-002

Status: Active

Year Funded: 2022

Amount awarded: $32,107

Investigator: Ronald Hak Long Li, DVM, PhD, DACVECC; Wan Khoon Avalene Tan, BVSc, DAVECC; Joshua A. Stern, DVM, PhD, DACVIM (Cardiology); University of California Davis